Pathogenesis of Rift Valley Fever Virus Aerosol Infection in STAT2 Knockout Hamsters

Area of Science:

• Virology
• Infectious Diseases
• Animal Models

Background:

• Rift Valley fever virus (RVFV) is an emerging zoonotic pathogen causing severe disease in humans and livestock.
• Aerosol transmission of RVFV poses significant risks, necessitating effective countermeasures.
• Current animal models for RVFV aerosol infection require high biosafety containment (BSL-3/4), limiting research accessibility.

Purpose of the Study:

• To establish and characterize a novel, accessible animal model for RVFV aerosol infection.
• To utilize a modified-live RVFV vaccine (MP-12) for safe induction of disease in a BSL-2 setting.
• To validate the utility of STAT2 knockout (KO) hamsters for studying RVFV pathogenesis and countermeasure efficacy.

Main Methods:

• Nose-only inhalation exposure of STAT2 KO hamsters to aerosolized RVFV MP-12 vaccine virus.
• Detection of RVFV in hepatic and other tissues post-inhalation.
• Analysis of clinical signs, blood chemistry, and hematological parameters.

Main Results:

• RVFV was detected in multiple tissues, including liver and spleen, 4-5 days after aerosol challenge.
• Significant alterations in liver disease markers and white blood cell counts were observed.
• The STAT2 KO hamster model exhibited pathological features consistent with RVFV infection in humans and other animal models.

Conclusions:

• STAT2 KO hamsters provide a viable BSL-2 model for RVFV inhalation studies.
• This model accurately reflects RVFV pathogenesis following aerosol exposure.
• The model supports the development and testing of antiviral and vaccine countermeasures against RVFV.